Microelectrode Array Insertion System using Ultrasonic Vibration to Improve Insertion Mechanics, Reduce Tissue Dimpling and Trauma, and Improve Placement Precision in the Neocortex

使用超声波振动的微电极阵列插入系统改善插入力学，减少组织凹陷和创伤，并提高新皮质的放置精度

• 批准号: 10268984
• 负责人: Maureen L. Mulvihill
• 金额: $ 142.35万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268984
• 关键词: Amputees; Animal Model; BRAIN initiative; Brain; Caliber; Cell Death; Chronic; Cicatrix; Clinical; Collaborations; Communication; Communities; Complex; Coupling; Data; Development; Devices; Dura Mater; Electrodes; Engineering; Equipment Malfunction; Exhibits; Feedback; Foreign Bodies; Frequencies; Goals; Hemorrhage; Human; Image; Implant; Implantation procedure; Implanted Electrodes; Incidence; Individual; Inflammation; Location; Magnetic Resonance Imaging; Manuals; Marketing; Mechanics; Medical; Medical Research; Methods; Microelectrodes; Motion; Neocortex; Neurologic; Neurons; Neurosciences Research; Operative Surgical Procedures; Outcome; Paraplegia; Patient Care; Penetration; Peripheral Nervous System; Phase; Polymers; Property; Proprioception; Prosthesis; Rattus; Resolution; Risk; Sales; Sensory; Shapes; Silicon; Site; Small Business Innovation Research Grant; Speed; Structure; Surface; System; Technology; Testing; Tissues; Trauma; Tungsten; Ultrafine; Ultrasonics; Validation; Work; base; brain machine interface; carbon fiber; commercialization; cranium; density; design; extracellular; flexibility; grasp; implantation; improved; improved outcome; in vivo; innovation; millimeter; minimally invasive; motor control; neural implant; neurotransmission; nonhuman primate; novel; pre-clinical; preservation; prosthesis control; relating to nervous system; response; success; tissue trauma; tool; two-photon; verification and validation; vibration

This Phase II SBIR further develops and tests a system that employs ultrasonic vibration to improve the insertion mechanics for multichannel penetrating electrode arrays. This proposal is in response to PA-18-871 BRAIN Initiative: Development, Optimization, and Validation of Novel Tools and Technologies for Neuroscience Research – including ‘Iterative refinement of such tools and technologies with the end-user community’. The long-term goal of Actuated Medical, Inc. is to develop technology enabling accurate placement of penetrating neural electrode arrays at target locations with minimal tissue trauma and displacement, ultimately paving the way for clinical use of neural implants. Penetrating neural implants provide direct access to extracellular neural signals across the central and peripheral nervous systems with both high temporal and spatial resolution. Unfortunately, the implantation of neural electrode arrays, commonly comprised of numerous closely spaced shanks, applies forces to neural tissue resulting in significant compression (dimpling), prohibiting uniform shank insertion, and increasing the risk of trauma, bleeding and inflammation at the implant site. These issues can increase the chronic foreign body response (FBR) leading to neural cell death, glial scaring, and device failure. Phase I demonstrated the ability to releasably grip and deliver ultrasonic vibration to a range of commercially available implant types, including floating-style arrays, resulting in reductions of insertion force and surface dimpling in bench studies of up to 80-90% for most implants tested. In vivo, ultrasonic vibration significantly reduced brain surface dimpling (~50%, p<0.01) and exhibited evidence of reduced bleeding, while preserving device function as evidenced by post implant neural recordings. Furthermore, preliminary work suggests significant potential for the ultrasonic vibration to improve insertion of ultrafine (8-15 µm) microwire arrays, as well as NeuroNexus’ Matrix platform arrays, one of the most delicate and complicated commercially-available implants. This Phase II SBIR expands use of the NeuralGlider inserter for inserting complex, fragile, and flexible penetrating neural electrode arrays using ultrasonic vibration to reduce insertion force, brain surface dimpling, tissue damage, and bleeding. The project uses a unique multi-institutional collaboration to obtain scientific data, supporting the benefits of the NeuralGlider insertion technology. Phase II hypothesis: Ultrasonic micro-vibration improves insertion accuracy and success, reduces insertion trauma, and improves recording outcomes for penetrating neural electrode arrays. Specific Aims: Aim 1 - Evaluate implantation trauma and inflammation response through 2-photon imaging and magnetic resonance imaging. Aim 2 - Demonstrate efficacy of NeuralGlider insertion approach for ultra-fine, ultra-high-density electrode array designs. Aim 3 - Integrate end user feedback, design upgrades for coupling options, and conduct Verification and Validation. Aim 4 - Demonstrate improved outcomes with micro-vibrated insertion.

第二阶段SBIR进一步开发和测试了一个系统，该系统采用超声波振动来改善 用于多通道穿透电极阵列的插入机构。本提案是对PA-18-871的回应 BRAIN倡议：开发，优化和验证新的工具和技术， 神经科学研究-包括“与最终用户一起迭代改进这些工具和技术” 社区'。Actuated Medical，Inc.的长期目标是开发一种技术， 将穿透性神经电极阵列放置在目标位置，组织创伤最小， 最终为神经植入物的临床应用铺平了道路。 穿透性神经植入物提供了直接进入细胞外神经信号通过中央和 具有高时间和空间分辨率的外周神经系统。不幸的是， 神经电极阵列通常由许多紧密间隔的柄部组成， 组织导致显著压缩（凹陷），阻止均匀的柄插入，并增加 植入部位的创伤、出血和炎症风险。这些问题可能会增加长期的外国 身体反应（FBR）导致神经细胞死亡、神经胶质瘢痕化和装置故障。第一阶段展示了 能够可释放地夹持并将超声振动传递到一系列市售植入物类型， 包括浮动式阵列，导致在台架研究中插入力和表面凹陷的减少， 对于大多数测试的植入物，高达80-90%。在体内，超声振动显著减少脑表面凹陷 （~ 50%，p<0.01），并显示出血减少的证据，同时保留器械功能，如 植入后的神经记录此外，初步工作表明，超声波的巨大潜力 振动，以改善超细（8-15 µm）微线阵列的插入，以及NeuroNexus的矩阵平台 阵列，其中一个最微妙和复杂的商业植入物。第二阶段SBIR扩展了 使用NeuralGlider插入器插入复杂、易碎和灵活的穿透性神经电极阵列 使用超声波振动来减小插入力、脑表面凹陷、组织损伤和出血。的 该项目采用独特的多机构合作来获取科学数据，支持 NeuralGlider插入技术。第二阶段假设：超声微振动提高插入精度 成功，减少插入创伤，并改善穿透神经电极的记录结果 阵具体目的：目的1 -通过双光子成像评价植入创伤和炎症反应 成像和磁共振成像。目的2 -证明NeuralGlider插入方法的有效性 用于超细、超高密度电极阵列设计。目标3 -整合最终用户反馈，设计升级 耦合选项，并进行验证和确认。目标4 -展示改善的结果， 微振动插入。